Correlation between Long-acting Thyroid Stimulator Protector Level and Thyroid 131I Uptake in Thyrotoxicosis

Out of 50 consecutive untreated patients with diffuse toxic goitre 15 showed long-acting thyroid stimulator (LATS), 30 showed LATS protector only, and five showed neither. LATS protector was present in all the patients with LATS. Infiltrative ophthalmopathy was less common in patients with LATS protector only (40%) than in patients with LATS also (67%), but the difference was not significant. There was a correlation between LATS protector level and thyroid ¹³¹I uptake rate factor (k₁), the coefficient (r) being 0·68 (P < 0·001). LATS level showed no such correlation. The results support the hypothesis that LATS protector is a pathogenic thyroid stimulator in patients with diffuse toxic goitre.     

Incidental thyroid carcinoma in thyrotoxic patients treated by surgery

BACKGROUND AND AIMS: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reported at different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed with surgery in our institution. METHODS: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997-2004, 70.7% were females and 29.3% were males. Among thyrotoxic patients 65.3% (n=245) had toxic multinodular goiter (TMG), 16.8% (n=63) had toxic adenoma (TA) and 17.9% (n=67) had Graves' disease. RESULTS: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) of Graves' disease patients had thyroid carcinoma. Histologic examination revealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle cell and 1 anaplastic carcinoma. CONCLUSION: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroid microcarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was not higher in subjects with Graves' disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects with thyrotoxicosis treated with surgery was similar to previous studies reported from different countries.     

Radioiodine treatment of multinodular non-toxic goitre.

OBJECTIVE--To investigate the long term effect of radioactive iodine on thyroid function and size in patients with non-toxic multinodular goitre. DESIGN--Consecutive patients with multinodular non-toxic goitre selected for radioactive iodine treatment and followed for a minimum of 12 months (median 48 months) after an intended dose of 3.7 MBq/g thyroid tissue corrected to a 100% uptake of iodine-131 in 24 hours. PATIENTS--69 patients with a growing multinodular non-toxic goitre causing local compression symptoms or cosmetic inconveniences. The treatment was chosen because of a high operative risk, previous thyroidectomy, or refusal to be operated on. MAIN OUTCOME MEASUREMENTS--Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 1, 2, 3, 6, and 12 months after treatment and then once a year. RESULTS--56 patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose and remaining euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (23-48) ml at 24 months in the 39 patients in whom this was measured during follow up. The median reduction was 40 (22-48) ml (60% reduction, p < 0.0001), half of which occurred within three months. Patients treated with two doses as well as those developing hypothyroidism and hyperthyroidism had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%, 95% confidence interval 4.8% to 38.4%). Side effects were few: three cases of hyperthyroidism and two cases of radiation thyroiditis. Only one patient was dissatisfied with the result; she was referred for operation six months after treatment. CONCLUSIONS--A substantial reduction in thyroid volume accompanied by a low incidence of hypothyroidism and few side effects makes the use of radioactive iodine an attractive alternative to surgery in selected cases of non-toxic multinodular goitre.     

Diagnosing amyloid goitre with thyroid aspiration biopsy

OBJECTIVE: The aim of the study was to evaluate the value of fine needle aspiration biopsy of the thyroid as a tool for diagnosing amyloid goitre and assess how amyloidosis affects thyroid tissue and thyroid function. METHODS: Clinical and laboratory evaluation of 50 patients with secondary systemic amyloidosis was done, and goitre was found in 38 of them. All 38 patients underwent thyroid aspiration biopsy. Tissue samples were stained with haematoxylin and eosin, May-Grünwald-Giemsa, crystal violet and Congo red. RESULTS: Of the 38 cases of amyloid goitre, 10 showed euthyroid sick syndrome, two showed primary hyperthyroidism, two showed hypothyroidism and one showed subacute thyroiditis. The serum levels of thyroid hormones and thyroid-stimulating hormone were normal in the remaining patients. Thirty-five of the 38 patients (92%) showed amyloidosis after thyroid aspiration. One of these patients had papillary carcinoma in addition to amyloid goitre. Ten patients underwent subtotal thyroidectomy, and one patient underwent total thyroidectomy after aspiration. Microscopic evaluation revealed that the thyroid parenchyma in all patients was largely replaced with amyloid and adipose tissue. CONCLUSION: Fine needle aspiration of the thyroid is a valuable and sensitive method for diagnosing amyloid goitre, especially because it is a safe and easily performed procedure. Further, amyloid goitre has no significant influence on thyroid function even when it causes extensive parenchyma replacement.     

Role of Thyroid Doppler in Differential Diagnosis of Thyrotoxicosis

ObjectiveTo evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis.MethodsConsecutive patients with thyrotoxicosis presenting to our center between June 2007 and March 2008 were included in the study. Clinical data were collected, and thyroid function tests including measurements of thyrotropin, total thyroxine, and total triiodothyronine were performed. Thyroid glands of all patients were evaluated with color-flow Doppler ultrasonography for size, vascularity, and peak systolic velocity of the inferior thyroid artery. Technetium Tc 99m pertechnetate scan was done when the diagnosis was not clear on the basis of clinical findings. Patients were divided into 2 groups for analysis: patients with destructive thyrotoxicosis and patients with Graves disease. Paired t tests and Fisher exact tests were used for statistical analysis.ResultsA total of 65 patients participated in the study; 31 had destructive thyrotoxicosis and 34 had Graves disease. Thyroid blood flow, as assessed by peak systolic velocity of the inferior thyroid artery, was significantly higher in patients with Graves disease than in patients with destructive thyroiditis (57.6 ± 13.1 cm/s vs 22.4 ± 5.4 cm/s; P < .05). All patients with destructive thyroiditis had low peak systolic velocity of the inferior thyroid artery, and 32 of 34 patients with Graves disease had high peak systolic velocity. Color-flow Doppler ultrasonography parameters correlated significantly with pertechnetate scan results, demonstrating a comparable sensitivity of 96% and specificity of 95%.ConclusionsDifferentiating Graves thyrotoxicosis from destructive thyrotoxicosis is essential for proper selection of therapy. Assessment of thyroid blood flow by color-flow Doppler ultrasonography is useful in this differentiation. (Endocr Pract. 2009;15:6-9)     

Sleepwalking Associated with Hyperthyroidism

ObjectiveTo report several cases of hyperthyroidism in patients presenting with the unusual symptom of sleepwalking and to discuss the possible pathophysiologic basis for this novel association.MethodsAfter encountering and reporting the first case of new-onset somnambulism in a patient presenting with thyrotoxicosis at our institution, we routinely inquired about the sleep history of patients with thyrotox-icosis, questioning both the patients and family members when applicable. Those patients who actually had sleepwalking episodes coinciding with the onset of thyrotoxi-cosis underwent close follow-up, and the relationship between the sleepwalking and the results of thyroid function tests was analyzed. In addition, we reviewed the literature on psychiatric disorders and sleep problems, and the pathophysiologic rationale for a cause-and-effect relationship is discussed.ResultsWe collected 8 cases of patients with new-onset sleepwalking episodes that coincided with the start of thyrotoxicosis. The disappearance of the sleepwalking with successful achievement of euthyroidism supports a cause-and-effect relationship. This hypothesis is further supported by the absence of a family history, the adult onset, and the relapse of sleepwalking in 2 of the patients when their thyrotoxicosis became poorly controlled as a result of noncompliance with medications and its subsequent disappearance with reachievement of euthyroidism. Of note, such a presentation was seen only in patients with thyrotoxicosis caused by diffuse toxic goiter or Graves’ disease and never in patients with other causes of thyro-toxicosis.ConclusionNew-onset sleepwalking could be caused by thyrotoxicosis or, more specifically, by thyrotoxicosis resulting from diffuse toxic goiter. The mechanism is hypothesized to be related to the combination of prolongation of non-rapid eye movement sleep and the associated fatigue. Specific inquiry about this unusual presentation of thyrotoxicosis is encouraged, and more studies are needed to confirm and evaluate its extent. (Endocr Pract. 2005;11:5-10)     

Serum long acting thyroid stimulator protector in pregnancy complicated by Graves' disease.

Activities of serum long acting thyroid stimulator protector were measured in a series of nine pregnancies in eight mothers who had Graves'' disease, one of whom had been successfully treated by surgery. In all but two instances the activities tended to decline as pregnancy progressed. After delivery activities rose in three out of five patients in whom these had disappeared in pregnancy and, as this occurred, the patients relapsed. In the two patients whose activities did not decline thyrotoxicosis persisted throughout pregnancy and after delivery. None of the nine babies in this study suffered from neonatal thyrotoxicosis because maternal activities of the thyroid stimulator protector, though high enough to induce Graves'' disease in adults, were not above the threshold for the induction of thyroid overactivity in neonates.     

Thyroid cancer in patients with hyperthyroidism

Thyroid cancer can be associated with thyrotoxicosis caused by Graves' disease, toxic multinodular goiter, or autonomously functioning thyroid adenoma. The objective of this study was to summarize current evidence regarding the association of thyroid cancer and hyperthyroidism, particularly with respect to the type of hyperthyroidism found in some patients, and whether this affects the outcome of the patient. A PubMed search was performed up to August 2011. Articles were identified using combinations of the following keywords/phrases: thyroid cancer, papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer, hyperthyroidism, Graves' disease, auto-nomous adenoma, toxic thyroid nodule, and toxic multinodular goiter. Original research papers, case reports, and review articles were included. We concluded that the incidence, as well as the prognosis of thyroid cancer associated with hyperthyroidism is a matter of debate. It seems that Graves' disease is associated with larger, multifocal, and potentially more aggressive thyroid cancer than single hot nodules or multinodular toxic goiter. Patients with Graves' and thyroid nodules are at higher risk to develop thyroid cancer compared to patients with diffuse goiter. Every suspicious nodule associated with hyperthyroidism should be evaluated carefully.     

Thyrotoxicosis induced by iodine contamination of food--a common unrecognised condition?

The incidence of thyrotoxicosis in northern Tasmania rose significantly in 1964, two years before an epidemic of iodine-induced thyrotoxicosis was precipitated by the addition of iodate to bread to prevent goitre. Each time older patients accounted for most of the increase. The 1964 increase was probably iodine-induced as the use of iodophor disinfectants on dairy farms, which causes iodine residues in milk, began in 1963 and a fall in the prevalence of goitre in young children suggested an increase in dietary iodine at about that time. A further small increase in thyrotoxicosis in 1971 may also have been iodine-induced as it followed an extension of the use of iodophors. Dietary iodine is rising substantially in many places because of high iodine levels in milk and the use of iodine compounds in automated bread making, and this may be causing unsuspected iodine-induced thyrotoxicosis. Dietary iodine should be monitored regularly and clinicans alerted to any rise. Contamination of common foods with iodine should be more strictly controlled.     

Atypical forms of hyperthyroidism

Except from well-known the most frequent reasons of the hyperthyroidism such as the Graves-Basedow disease, multinodular goitre and the autonomous adenoma we should also remember the other rarer illnesses leading to the excess of thyroid hormones in the serum. Authors presented the problem of atypical forms of thyrotoxicosis which run without the overproduction of thyroid hormones and are characterized by low 24 h 131 J uptake by the thyroid gland. So called masks of hyperthyroidism such as apathetic, neuromuscular, gastrointestinal and cardiovascular forms were also discussed in the article.     

Diazepam and Tests of Thyroid Function

The effect of diazepam on thyroid function tests was examined in 12 euthyroid patients requiring the drug for psychiatric reasons and in six patients with thyrotoxicosis. Assessment was made before and after four weeks'' therapy.There was no significant difference in results from tests of thyroid iodide trapping and binding (thyroid radioiodine uptake, thyroid clearance, and absolute iodine uptake) except in the one-hour thyroid uptake in the euthyroid group, which was increased after diazepam. This increase occurred without alteration in serum thyroid stimulating hormone levels. No change occurred in either group in tests of thyroid hormone release (protein-bound iodine, T-3 resin uptake, or Thyopac-3 and free thyroxine index).Patients with suspected thyroid disease who are taking diazepam do not need to stop therapy while their thyroid status is being determined.     

Recurrent Thyrotoxicosis after Subtotal Thyroidectomy

A study of patients with recurrent thyrotoxicosis after subtotal thyroidectomy has shown that the operation has a profound effect on the natural history of Graves''s disease. It is followed by pronounced changes in the immunological features of the disease, with a fall in the prevalence of serum thyroid autoantibodies, including the long-acting thyroid stimulator. Thyroid suppression returns to normal in 70% of patients. The treatment produces two populations of patients. In the larger group there is a permanent remission of the disease process. In the smaller group the disease process persists and, consequently, recurrent hyperthyroidism may develop. The mechanism of the change in the larger group of patients probably has an immunological basis.     

Late-onset thyrotoxicosis after the cessation of amiodarone

IntroductionAmiodarone is a highly effective antiarrhythmic-drug with well recognized toxic side-effects. The effects of the drug late in patients with atrial fibrillation (AF) is not well described.Methods and resultsWe present a single centre prospectively collected series of patients with thyrotoxicosis occurring late after the cessation of amiodarone. Between 2006 and 2018, 8 patients were identified with amiodarone induced thyrotoxicosis (AIT). Amiodarone was prescribed for AF in 7 patients and ventricular tachycardia in 1 patient. Mean duration of therapy was 329 [42–1092] days, mean dose of 200 ± 103.5 mg/day. Amiodarone use was short term (<140 days) in 4 of the 8 cases, with one treated for 42 days. Patients presented with symptoms including weight loss, tremors, palpitations, AF, sweats all indicative of AIT at a median of 347 [60–967] days post cessation. Thyroid function testing confirmed suppressed thyroid stimulating hormone and elevated T levels in all patients. Nuclear thyroid imaging in all cases demonstrated low uptake of iodine indicative of Type II AIT. All patients recovered following pharmaceutical treatment with Carbimazole and Prednisolone.ConclusionsWe describe a series of patients with late thyrotoxicosis after exposure to amiodarone. Our findings highlight the need for a high-index of clinical suspicion for AIT regardless of treatment duration or time after cessation of amiodarone.     

Graves' disease: immunological and immunogenetic indicators of relapse

The use of measurements of antibody to the thyroid stimulating hormone receptor and HLA-DR3 phenotype for predicting relapse of hyperthyroidism in patients with Graves'' disease receiving medical treatment is controversial. Fifty eight new patients with Graves'' disease were followed up prospectively for up to 96 months after treatment with antithyroid drugs for 12 months. The presence of antibody to the thyroid stimulating hormone receptor before the start of treatment, measured as immunoglobulins inhibiting binding of thyroid stimulating hormone, was not associated with relapse. Patients who remained positive for antibodies after treatment tended to relapse within six months, but no relation with long term relapse was found. HLA-Cw7 but not HLA-DR3 was significantly associated with relapse. The presence of HLA-DR4 was significantly associated with remission and with absence of antibodies to thyroid stimulating hormone receptor. HLA-DR4 may therefore protect against relapse of thyrotoxicosis by immunomodulation triggered by antithyroid drugs, which results in the synthesis of antibodies to the thyroid stimulating hormone receptor being inhibited.     

Management of Thyrotoxicosis Among General Practitioners in Trinidad Compared with 2016 American Thyroid Association Guidelines for Hyperthyroidism

Objective: A previous Trinidadian survey highlighted the investigative and therapeutic approaches selected by general practitioners (GPs) in managing thyrotoxicosis. The main objective of this study was to compare practice with existing guidelines.Methods: In this cross-sectional study a pretested de novo questionnaire was self-administered to GPs throughout Trinidad. The survey evaluated GPs' choices in management of thyrotoxicosis cases and compared their responses to the 2016 American Thyroid Association guidelines as well as with those previously reported locally.Results: A total of 159 completed questionnaires were analyzed (59% response rate). Thyroid stimulating hormone was the preferred (94%) biochemical test to confirm thyrotoxicosis etiology. A combination of ultra-sound and thyroid scintigraphy, thyroid ultrasound alone, and scintigraphy only were the testing options selected by 41%, 38%, and 12%, respectively. Generally medical therapy with antithyroid drugs was the preferred treatment option with 86% of respondents selecting this option for the index case of newly diagnosed female Graves disease. The greatest proportion of respondents that selected radioactive iodine (RAI) was 35% for both the index case as well as the male equivalent. Surgery was the most popular option at 25% for patients with a toxic multinodular goiter. Having access to RAI and scintigraphy was reported by 32% and 28%, respectively.Conclusion: GPs appear to be constrained to making rational choices based upon availability rather than what the guidelines recommend. In the absence of formal continuing medical education for GPs on thyrotoxicosis, dissemination of guidelines at the primary care level may reduce this gap.Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drugs; CME = continued medical education; GP = general practitioner; RAI = radioactive iodine; SURG = surgery; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Clinical Characteristics and Outcome of Thyroid Storm: A Case Series and Review of Neuropsychiatric Derangements in Thyrotoxicosis

ObjectiveThe objectives of this study were (1) to describe the presentation, demographics, and clinical course of patients admitted for thyroid storm, and (2) to identify factors associated with mortality.MethodsA retrospective review of subjects admitted to a single academic hospital from 2006 through 2011 was conducted. Medical records for all patients who were admitted with a diagnosis of thyrotoxicosis were systematically reviewed for clinical features of thyroid storm.ResultsA total of 28 cases were identified. Thyroid storm was the first clinical presentation of thyrotoxicosis in 13 patients (46.4%). Noncompliance with treatment was a major trigger in previously diagnosed patients, followed by infection. The mortality rate was 25% in this series. Cardiac manifestations were predominant, with > 60% of patients having severe tachycardia (heart rate > 140 beats per minunte) and/or atrial fibrillation. Although central nervous system (CNS) involvement was less frequent (n = 8, 28.6%), CNS derangement of worse than mild severity was statistically associated with mortality (P = .021). There was good agreement between the Burch-Wartofsky Point Scale and Japanese Thyroid Association criteria in the diagnosis of thyroid storm in this study cohort.ConclusionThyroid storm was the first presentation of thyrotoxicosis in a significant proportion of patients, highlighting the importance of a high index of suspicion in an appropriate clinical context. The presence of neuropsychiatric manifestations appeared to portend greater risk of mortality. Prevailing evidence suggests that there are complex interactions between thyroid hormones and neurotransmitter circuits in the pathogenesis of CNS symptomology in thyrotoxicosis. (Endocr Pract. 2015;21:182-189)     

Genetic Factors in Hashimoto's Struma

It has previously been established that there is a significant history of thyroid disorders in families of patients with Hashimoto''s struma or chronic thyroiditis. In the present study, 99 relatives of 20 patients with Hashimoto''s struma or chronic thyroiditis were studied with regard to the incidence of circulating thyroid autoantibodies; 42 of these 99 relatives were found to have such antibodies. Twenty of the 99 relatives were shown to have thyroid abnormalities (chiefly goitre); of this group of 20, antibodies were found in 12. In the remaining 79 persons (who had no clinical evidence of thyroid disease), 30 were found to have circulating antithyroid antibodies. The incidence of such antibodies among these relatives is very significantly greater than in the general population.From these and other similar studies, there is strong evidence favouring a genetic predisposition for Hashimoto''s struma and chronic thyroiditis. The mode of inheritance is not yet established, and the pathogenesis of the disease has not yet been elucidated.     

Clinical applications of assays for thyrotropin-receptor antibodies in Graves' disease.

Graves'' disease is characterized by hyperthyroidism, diffuse goitre, infiltrative ophthalmopathy and, rarely, pretibial myxedema. In 1956 a substance capable of prolonged thyroid stimulation was discovered in the serum of some patients with Graves'' disease and termed long-acting thyroid stimulator (LATS). It was shown to be an antibody that could interact with the receptor for thyroid-stimulating hormone (TSH). The term LATS is usually reserved for the activity measured in a laborious in-vivo bioassay in mice. Today the activity of TSH-receptor antibodies (TSH-R Ab) can be measured by in-vitro bioassays or by radioreceptor assays. These assays are now becoming commercially available. TSH-R Ab assays may be useful in predicting the response to therapy for Graves'' disease, investigating euthyroid ophthalmopathy and predicting the likelihood of neonatal hyperthyroidism.     

Hyperthyroidism—a Disease of Old Age?

In a three-year project in which thyroid studies were undertaken for broad indications 49 cases of thyrotoxicosis were diagnosed; 28 of these patients were 60 years of age or older. Sixteen of these older patients had different forms of atypical thyrotoxicosis, and most were completely without the usual symptoms of the condition. It is concluded that thyrotoxicosis is more frequent in persons over 60 than in younger persons. Many older patients have various forms of masked thyrotoxicosis, and in many cases the correct diagnosis can be made only by undertaking thyroid studies on very wide indications.     

Graves’ disease: Hereditary peculiarities and effect of selection on its prevalence population

The features of genetic determination and natural selection of diffuse toxic goiter (DTG) are studied on the basis of the clinical and genealogical data obtained from 242 patients with thyrotoxicosis and from obstetric anamneses of 2105 healthy women and 369 women with thyrotoxicosis. On the basis of the results of genetic analysis, the conformity of thyrotoxicosis inheritance to the alternative model parameters is revealed. In this model, the penetrance of homozygotes was 78.8%, and the penetrance of heterozygotes was 17.3%. It is shown that, in the population of Kharkiv oblast, the frequency of the gene of predisposition to thyrotoxicosis has grown 0.8% per generation.